Streamlined Catalytic Enantioselective Synthesis of α‑Substituted β,γ-Unsaturated Ketones and Either of the Corresponding Tertiary Homoallylic Alcohol Diastereomers

A widely applicable,
practical, and scalable strategy for efficient
and enantioselective synthesis of β,γ-unsaturated ketones
that contain an α-stereogenic center is disclosed. Accordingly,
aryl, heteroaryl, alkynyl, alkenyl, allyl, or alkyl ketones that contain
an α-stereogenic carbon with an alkyl, an aryl, a benzyloxy,
or a siloxy moiety can be generated from readily available starting
materials and by the use of commercially available chiral ligands
in 52–96% yield and 93:7 to >99:1 enantiomeric ratio. To
develop
the new method, conditions were identified so that high enantioselectivity
would be attained and the resulting α-substituted NH-ketimines,
wherein there is strong CN → B­(pin) coordination, would
not epimerize before conversion to the derived ketone by hydrolysis.
It is demonstrated that the ketone products can be converted to an
assortment of homoallylic tertiary alcohols in 70–96% yield
and 92:8 to >98:2 drin either diastereomeric formby
reactions with alkyl-, aryl-, heteroaryl-, allyl-, vinyl-, alkynyl-,
or propargyl-metal reagents. The utility of the approach is highlighted
through transformations that furnish other desirable derivatives and
a concise synthesis route affording more than a gram of a major fragment
of anti-HIV agents rubriflordilactones A and B and a specific stereoisomeric
analogue.